Human post heparin plasma contains lipoprotein lipase (LPL) and hepatic lipase (HL), two major enzymes involved in lipoprotein metabolism. Studies were undertaken to further delineate the role of HL in lipid metabolism. A plasma activator of HL was isolated, and shown to be apolipoprotein A-II. A major substrate for HL is HDL, and HL appears to play a major role in the catabolism of the lipid component of HDL2. The cofactor function of apoA-II for HL, is analoagous to the cofactor function of apoC-II for LPL. Studies of patients with primary biliary cirrhosis revealed two groups of patients. One group had decreased HL activity, high HDL, and increased apoA-I and apoA-II; the second group had decreased HDL, and an increase in a new lipoprotein, LpX. Studies have also been initiated on the purification of HL, and the production of monoclonal antibodies to HL.